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Purpose: This study aimed to examine the incidence of incisional hernia (IH) in elective laparoscopic colorectal surgery (LC) using regulated computed tomography (CT) images intervals every 6 months. Methods: We retrospectively examined the diagnosis of IH in patients who underwent LC for colorectal cancer at Kansai Medical University Hospital from January 2014 to August 2018. The diagnosis of IH was defined as loss of continuity of the fascia in the axial CT images. Results: 470 patients were included in the analysis. IH was diagnosed in 47 cases at 1 year after LC. The IH size was 7.8 cm2 [1.3–55.6] . In total, 38 patients with IH underwent CT examination 6 months after LC, and 37 were already diagnosed with IH. The IH size was 4.1 cm2 [0–58.9]. The IH size increased in 17 cases between 6 months and 1 year postoperatively, and in 1 case, a new IH occurred. 47%(18/38) of them continued to grow until 1 year after LC. A multivariate analysis was performed on the risk of IH occurrence. SSI was most significantly associated with IH occurrence (OR:5.28 [2.14–13.05], p=0.0003). Conclusion: In previous reports, IH was evaluated mainly by clinical symptoms, but in this study, CT was used to investigate the occurrence of IH. Therefore, we clarified that we were able to find IH while it is still small by CT taken regularly.

A 75-year-old woman was treated with TC plus Bev for cancer of unknown primary. During treatment, she presented to the clinic with chief complaints of general malaise and anorexia. On presentation, abdominal distention and upper abdominal tenderness were noted, and sepsis was suspected. A thoracoabdominal CT scan revealed prominent intramural emphysema and mesenteric gas in the ascending colon. An emergency laparotomy was performed for suspected pneumatosis intestinalis non-obstructive intestinal ischemia. However, no intra-abdominal contamination or ischemic changes were observed intraoperatively. Histological examination revealed a small adenocarcinoma on the serous surface of the ascending colon, and immunochemical staining confirmed the diagnosis of serous adenocarcinoma as the patient's primary cancer. This report describes a case in which the patient achieved long-term survival after diagnosis. It also emphasizes the importance of identifying the subset of patients with cancer of unknown primary who have a good prognosis in order to provide appropriate treatment.

Objective: The aim of this study was to compare the scar quality associated with different types of subcuticular suture techniques: running or interrupted. Summary of Background Data: Subcuticular suture is a preferred skin closure method even in gastrointestinal surgery. Two methods for subcuticular suture are used: running or interrupted sutures. Methods: Inclusion criteria were as follows: age ≥ 20 years; American Society of Anesthesiologists performance status 1 to 3; histologically proven adenocarcinoma of the stomach; no evidence of distant metastases or disease considered unresectable; no prior upper abdominal surgery; no uncontrolled infections, diabetes, or cardiac disease; and adequate renal function. Patients were randomly assigned to running subcuticular suture or interrupted subcuticular suture. Scar areas were calculated using a digital photograph calculator at about 7 months after surgery. The observer scar assessment scale (OSAS) was used for scar assessment. Results: Between April 10, 2009, and February 28, 2012, 220 patients were enrolled into this study and 201 patients were evaluated. There was no difference in scar area between the interrupted group and the running group [0.97 cm2 (95% CI: 0.73–1.21) in the interrupted group and 1.17 cm2 (95% CI: 0.91–1.42, P = 0.27) in the running group]. Three observers performed the OSAS, for which no significant difference was detected across the closure groups. Conclusions: There were no significant differences in cosmetic outcomes between running and interrupted subcuticular sutures. The final decision about the choice of method should be made balancing surgeon needs (time-saving with running) and surgeon techniques (running might be difficult).

Introduction The increased visceral fat in patients with obesity can increase the technical difficulty of surgery. This study was performed to evaluate a preoperative 20-day very low-calorie diet for obesity before laparoscopic gastrectomy for gastric cancer. Methods This prospective single-center study involved patients with obesity who were planning to undergo laparoscopic gastrectomy for gastric cancer. Obesity was defined according to the Japanese criteria: BMI ≥25 kg/m2 or waist circumference ≥85 cm in men and ≥90 cm in women. The patients underwent a preoperative 20-day very low-calorie diet and received nutritional counseling. Weight loss, body composition, visceral fat mass, and operative outcomes were evaluated. Results Thirty-three patients were enrolled from September 2013 to August 2015. Their median age was 71 years, and 78.8% were men. Their median bodyweight and BMI were 72.3 kg (range, 53.8-82.5 kg) and 26.0 kg/m2 (range, 23.5-31.0 kg/m2 ), respectively. The patients achieved a mean weight loss of 4.5% (95% confidence interval [CI]: 3.8-5.1), corresponding to 3.2 kg (95%CI: 2.7-3.7 kg). Body fat mass was significantly decreased by a mean of 2.5 kg (95%CI: 1.9-3.1), whereas skeletal muscle mass was unaffected (mean: -0.20 kg [95%CI: -0.55-0.15]). The visceral fat mass reduction rate was high as 16.8% (range, 11.6%-22.0%). All patients underwent laparoscopic gastrectomy as planned. Severe postoperative morbidity (Clavien-Dindo grade ≥III) was seen in only one patient (3.0%). Conclusion The preoperative 20-day very low-calorie diet weight loss program is promising for the treatment of obesity before laparoscopic gastrectomy for gastric cancer.

Background We recently selected double-pedicled free jejunal transfer for reconstruction of pharyngolaryngoesophagectomy to reduce the vascular thrombosis-induced necrosis in free jejunal transfer. We herein report our experience with this procedure. Methods Single-pedicled free jejunal transfer for reconstruction of pharyngolaryngoesophagectomy was performed from January 2006 to November 2013, and double-pedicled free jejunal transfer (i.e. two pairs of jejunal arteriovenous anastomoses) was performed from December 2013 to December 2016 in Kansai Medical University Hospital. We compared the perioperative outcomes and complications between these two procedures. Results Sixty-two patients (58 men, 4 women; median age, 66 years; age range, 51–83 years) underwent single-pedicled free jejunal transfer. Twenty-eight patients (25 men, 3 women; median age, 70 years; age range, 47–84 years) underwent double-pedicled free jejunal transfer. Twenty-eight patients received preoperative treatments. Table 1 shows the perioperative outcomes and complications. Conclusion No thrombus of the free jejunum occurred, no anastomotic leakage occurred, and all flaps survived in the double-pedicled free jejunal transfer group. We believe that double-pedicled free jejunal transfer for reconstruction of pharyngolaryngoesophagectomy is a reliable and useful procedure. Disclosure All authors have declared no conflicts of interest.

Aggressive angiomyxoma is an uncommon mesenchymal tumor that mostly involves the pelvic and perineal regions in young women.We herein report an extremely rare case of aggressive angiomyxoma in a 75-year-old man. The patient had undergone follow-up for an intraductal papillary mucinous neoplasm.In September 2015, CT detected a tumor measuring 33 mm in diameter around the pelvis, and the tumor showed gradual increase in size.MRI revealed a relatively sharply marginated tumor with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.For treatment and diagnosis, we laparoscopically resected the tumor. Histopathologically, the specimen showed spindle tumor cells within a myxoid background and vascular structures.The tumor was diagnosed as aggressive angiomyxoma, and surgical margins were negative for tumor cells. The patient is currently doing well without any signs of recurrence as of 18 months postoperatively.

We herein report 2 cases of successful surgical treatment of reconstructed gastric tube-bronchial fistulas caused by leakage after esophagectomy for esophageal cancer. One patient was a 56-year-old man who developed a reconstructed gastric tube-bronchial fistula, and the fistula was closed by conservative treatment. However, he developed pneumonia on postoperative day 117, and the reconstructed gastric tube-bronchial fistula was found to have recurred. Fibrin glue was endoscopically injected into the fistula, but this treatment was unsuccessful. The other patient was a 60-year-old man who developed a reconstructed gastric tube-bronchial fistula and severe pneumonia, and his condition did not improve by conservative treatment. We performed a reoperation for both patients using a pedunculated latissimus dorsi flap, and both patients recovered well.

Introduction The increased visceral fat in patients with obesity can increase the technical difficulty of surgery. This study was performed to evaluate a preoperative 20‐day very low‐calorie diet for obesity before laparoscopic gastrectomy for gastric cancer. Methods This prospective single‐center study involved patients with obesity who were planning to undergo laparoscopic gastrectomy for gastric cancer. Obesity was defined according to the Japanese criteria: BMI ≥25 kg/m2 or waist circumference ≥85 cm in men and ≥90 cm in women. The patients underwent a preoperative 20‐day very low‐calorie diet and received nutritional counseling. Weight loss, body composition, visceral fat mass, and operative outcomes were evaluated. Results Thirty‐three patients were enrolled from September 2013 to August 2015. Their median age was 71 years, and 78.8% were men. Their median bodyweight and BMI were 72.3 kg (range, 53.8–82.5 kg) and 26.0 kg/m2 (range, 23.5–31.0 kg/m2), respectively. The patients achieved a mean weight loss of 4.5% (95% confidence interval [CI]: 3.8–5.1), corresponding to 3.2 kg (95%CI: 2.7–3.7 kg). Body fat mass was significantly decreased by a mean of 2.5 kg (95%CI: 1.9–3.1), whereas skeletal muscle mass was unaffected (mean: −0.20 kg [95%CI: −0.55–0.15]). The visceral fat mass reduction rate was high as 16.8% (range, 11.6%–22.0%). All patients underwent laparoscopic gastrectomy as planned. Severe postoperative morbidity (Clavien–Dindo grade ≥III) was seen in only one patient (3.0%). Conclusion The preoperative 20‐day very low‐calorie diet weight loss program is promising for the treatment of obesity before laparoscopic gastrectomy for gastric cancer.

Background Chylothorax after thoracic surgery is initially managed conservatively, but when persistent high-output chylothorax (> 1000 mL/day) is managed conservatively, the mortality rate exceeds 50%. The objective of this study was to examine the clinical results of thoracic duct embolization (TDE) in cases of chylothorax after esophagectomy for esophageal cancer. Methods The data of 9 patients (7 men, 2 women) whounderwent TDE for persistent high-output chylothorax after esophagectomy for esophageal cancer were gathered retrospectively. Lymphangiography was used to identify the supply route of lymphatic fluid from the lumbar lymphatics to the leakage site and lipiodol extravasation and its site. Transcatheter thoracic ductography was used to identify communication between the thoracic duct and the leakage site and extravasation of the iodinated contrast agent. TDE was performed by percutaneous transabdominal approach to cut off the supply route. The technical success and clinical success (drainage volume ≥ 10mL/kg/day within 7 days after TDE) of TDE were evaluated. Results The technical and clinical success rates of TDE were 89.9%, with no serious complications observed. In 44% of patients, the thoracic duct had ruptured. In the other 56%, the ruptured was in a collateral route bypassing the thoracic duct; the leaking lymphatic fluid was supplied without passing through the thoracic duct in 50% of these patients, but clinical success was achieved even in such patients. Conclusion TDE was found to be a safe method of treatment, with no serious complications. Disclosure All authors have declared no conflicts of interest.

We report a duodenal stump reinforcement procedure in laparoscopic distal gastrectomy with Roux-en-Y reconstruction.We retrospectively reviewed the data of 223 patients who underwent laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer. We compared 2 groups: group NR (not reinforced, n=102, June 2009 to December 2011) when we did not perform reinforcement of the duodenal stump, and group R (reinforced, n=121, January 2012 to July 2014) when we did the reinforcement. The duodenum was divided with an endoscopic linear stapler. In group R, the duodenal staple line was reinforced by hand-sewn Lembert's sutures.There were no significant differences between group NR and R in patients' characteristics. Duodenal stump leakage occurred in 2 patients in group NR (2.0%). By contrast, in R group, no patients had duodenal stump leakage or fistula.Duodenal stump leakage can be avoided by using reinforcement with Lembert's sutures.

Background IgG4-related disease (IgG4-RD) is a systemic disease characterized by fibrosing inflammation with an abundance of IgG4-positive plasma cells. IgG4-RD has been found to affect various organs. Many cases of IgG4-RD affecting the extrapancreatic organs have been reported in patients without pancreatic lesions. Methods Sclerosing esophagitis with IgG4-positive plasma cell infiltration is very rare disease. We report a case of esophageal benign stricture that was difficult to diagonose. Results A 76-year-old woman had been experiencing slight difficulty in swallowing in the 3 years prior to this presentation. Her dysphagia had progressed and she began to vomit frequently after meals and lost weight while hospitalized after surgery for cervical cancer. Esophagogastroduodenoscopy and an esophagram showed circumferential erosion and a stricture of the thoracic esophagus. No malignant cells were identified. However, because it was difficult to exclude a malignant tumor, she underwent esophageal resection. The resected specimen showed stricture with mucosal erosion and transmural wall hypertrophy. On histological examination, transmural hyperplasia consisting of inflammatory granulation tissue with abundant infiltration of IgG4-positive plasma cells and lymphocytes was observed. Conclusion A probable diagnosis of IgG4-related disease was made because comprehensive diagnostic criteria for this condition were met. IgG4-related esophageal disease presenting as esophageal lesions alone is very rare. Disclosure All authors have declared no conflicts of interest.

Summary(NZW × BXSB)F1 mice (W/BF1 mice) have been reported to be a type of autoimmune-prone mice, showing symptoms of proteinuria, anti-DNA antibodies and anti-platelet antibodies. In this paper, we report that W/BF1 mice show hyperproduction of tumour necrosis factor (TNF)-α, responding to lipopolysaccharide (LPS) in comparison with normal mice, resulting in induction of death. In normal mice, monocytes/macrophages (Mo/MØ) are the main producer of TNF-α, while both Mo/MØ and dendritic cells (DCs) produce TNF-α in W/BF1 mice. Because the number of DCs is higher in W/BF1 mice, the main producers of TNF-α in W/BF1 mice are thought to be DCs. Moreover, administration of anti-TNF-α antibodies rescued the W/BF1 mice from death induced by LPS, suggesting that TNF-α is crucial for the effect of LPS. Although there is no significant difference in the expression of Toll-like receptor-4 (TLR-4) on DCs between B6 and W/BF1 mice, nuclear factor kappa b activity of DCs from W/BF1 mice is augmented under stimulation of LPS in comparison with that of normal mice. These results suggest that the signal transduction from TLR-4 is augmented in W/BF1 mice in comparison with normal mice, resulting in the hyperproduction of TNF-α and reduced survival rate. The results also suggest that not only the quantity of endotoxin, but also the host conditions, the facility to translate signal from TLR, and so on, could reflect the degree of bacterial infections and prognosis.

Cytoglobin (Cygb) is a recently discovered member of the vertebrate globin family, which includes probably most extensively studied proteins, hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb). It has been reported that Cygb is expressed ubiquitously at the mRNA or protein level. However, details of the distribution of Cygb in the various tissues have hitherto been unclear. In this experiment, we clarified the distribution of Cygb in various human tissues by immunohistochemical staining. First, we prepared a rabbit anti human Cygb polyclonal antibody. Using the antibody, we stained a tissue array slide containing 60 normal tissues from 40 human organs. We confirmed the staining patterns of the antibodies in these various tissues using autopsy samples from our university. In general, Cygb is positive in the epithelial cells, hepatocytes, pancreatic acinar cells, cardiomyocytes and skeletal muscle but rarely so in cells in the interstitial tissues. Cytoglobin is usually positive in the cytoplasm, but is also positive in the nucleus in some hepatocytes. In contrast, Cygb is negative in the smooth muscle. The distribution of Cygb could suggest its roles.

The collection of bone marrow cells (BMCs) using a perfusion method has been advantageous not only because of the low contamination of BMCs with T cells from the peripheral blood but also the enrichment of stromal cells, which support hemopoiesis. Before the application of this new method to humans, its safety needed to be confirmed using cynomolgus monkeys. We therefore performed the perfusion method on more than 100 cynomolgus monkeys using the long bones (such as the humerus and femur) and also the iliac bones (for human application); in the more than 150 trials to date, there have been no accidental deaths. Furthermore, the technical safety of a new method for the intra-bone marrow (IBM) injection of BMCs (termed IBM-bone marrow transplantation) has also been confirmed using 30 monkeys. Disclosure of potential conflicts of interest is found at the end of this article.

We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells (CD4− cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4− cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell-depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4+ cell-depleted spleen cells (CD4− cells) or CD8+ cell-depleted spleen cells (CD8− cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8− cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4− cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4− cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4− cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4− cells could become a new strategy for the treatment of solid tumors.

We have established a new method for allogeneic pancreatic islet (PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1A(l), RT1B(l)), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1A(n), RT1B(n)) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of '9 Gy+IBM'(10/10 accepted), '9 Gy+PV'(7/10 accepted), '9 Gy+IV'(0/7 accepted), '9 Gy+PV+IBM'(8/8 accepted), '8.5 Gy+IBM'(4/9 accepted), '8.5 Gy+PV'(0/7 accepted), '8.5 Gy+IV'(0/7 accepted), '8.5 Gy+PV+IBM'(9/12 accepted), '8 Gy+IBM'(2/10 accepted) and '8 Gy+PV+IBM'(2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable strategy.

Choriocarcinomas usually develop in the uterus and ovaries in the female, being extremely rare in the extragenital organs in the male. Extragenital choriocarcinomas in the male usually develop in the mediastinum or retroperitoneum. The frequency of choriocarcinoma in the urinary bladder is extremely low. The purpose of the present paper was to report an autopsy case of choriocarcinoma in the urinary bladder in the male. An 81-year-old male patient with macrohematuria was first diagnosed with transitional cell carcinoma (TCC). At autopsy a hemorrhagic necrotic tumor, which was found in the urinary bladder with metastatic lesions in the lungs, was diagnosed as choriocarcinoma microscopically. There was no evidence for choriocarcinoma derived from any other organs than the urinary bladder, although there were metastatic lesions in both lungs and the direct invasion into the prostate. From these findings it is concluded that the tumor was a primary choriocarcinoma in the urinary bladder in a male patient. Choriocarcinoma of the urinary bladder is very rare, but the prognosis is extremely poor in comparison with TCC even in the urinary bladder. Therefore, it is essential to clearly discriminate between choriocarcinomas and TCC.

Cisplatin, which is a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. This article examines whether G-CSF and/or M-CSF rescues mice from renal failure induced by cisplatin. BALB/c mice received intraperitoneal injections with or without G-CSF and/or M-CSF for 5 d (from day -5 to day -1). The day after the last injection of G-CSF and/or M-CSF (day 0), the mice received an intraperitoneal injection of cisplatin. When pretreated with G-CSF or G-CSF + M-CSF, the mice showed longer survival and lower serum creatinine and blood urea nitrogen levels than mice that had been received injections of M-CSF or saline. Histologically, pretreatment with G-CSF or G-CSF + M-CSF attenuated the damage to renal tubules induced by cisplatin. BALB/c mice that had received a transplant of bone marrow cells of enhanced green fluorescent protein (EGFP)-transgenic mice ([EGFP-->BALB/c] mice) were treated with or without G-CSF and/or M-CSF, followed by injection of cisplatin as well as above. [EGFP-->BALB/c] mice that were treated with G-CSF or G-CSF + M-CSF showed a significantly higher number of EGFP(+) tubular epithelial cells in the kidney than mice that were treated with only M-CSF or saline. These results suggest that bone marrow cells mobilized by G-CSF accelerate the improvement in renal functions and prevent the renal tubular injury induced by cisplatin and that M-CSF enhances the effects of G-CSF.

For patients who have undergone gastrectomy for gastric cancer, a follow-up by upper gastrointestinal endoscopy is required. However, it is sometimes very difficult to observe the remnant stomach due to a significant amount of residual food. We evaluated the reduction of food residue by drinking water as preparation before upper gastrointestinal endoscopy in postpartial gastrectomy patients. We compared two groups. In the water group, patients drank 500 mL water after dinner on the evening before endoscopy, and on the day of endoscopy they drank 350 mL water before the examination. In the control group, patients drank nothing after dinner, and nothing on the day of endoscopy. In the water group, food residue in the remnant stomach was reduced. In patients who underwent proximal gastrectomy or pylorus-preserving gastrectomy, food residue in the remnant stomach was not reduced by drinking water. However, in patients with distal gastrectomy, food residue was reduced by drinking water. Drinking water before upper gastrointestinal endoscopy is safe with no risk of complications, and our results suggested that drinking water effectively reduced food residue in the remnant stomach before endoscopic examination.

The aim of the study was to evaluate the potential advantages of the ultrasonic scalpel compared with the conventional technique in gastric cancer surgery.Patients with resectable adenocarcinoma of the stomach were randomly assigned to ultrasonic scalpel or conventional technique. We used the HARMONIC FOCUS (Ethicon Endo-Surgery, Inc.) as ultrasonic scalpel.Between February 2010 and December 2010, 60 patients with resectable gastric cancer were enrolled into the study. Operative time was significantly shorter with the ultrasonic arm than with the conventional arm (median 238.5 vs. 300.5 min; P = 0.0004). Blood loss was also significantly lower in the ultrasonic arm than in the conventional arm (median 351.0 vs. 569.5 ml; P = 0.016). Clavien-Dindo grades of postoperative complications were similar in the two groups. From a questionnaire survey of operators, the ultrasonic scalpel significantly reduced the stress of lymph node dissection (3.67 vs. 2.87; P = 0.0006). However, in assisting surgeons, the contributions to surgery, study, and technical improvement of the ultrasonic group were lower than in the conventional group.This study shows that the ultrasonic scalpel is a reliable and safe tool for open gastric cancer surgery.

It is difficult to perform the staging of laparoscopy within the restricted time at a high-volume center. We thus started between-hospital cooperation as of April 2008. In this hospital cooperation, we perform surgery after laparoscopic examination at a cooperating hospital.Staging laparoscopy was indicated for patients with T3 or T4 gastric cancer. These patients underwent staging laparoscopy at Maki Hospital before their scheduled surgery at our own hospital.Between April 2008 and January 2009, 14 patients underwent staging laparoscopy. We received the laparoscopic findings and confirmed the histopathological examination for median 11 days. The median duration from the day that we requested Maki Hospital to the day that patients underwent surgery was 34 days. No patient had laparoscopic complications. Of the 14 patients, 4 patients had peritoneal metastasis. Ten patients did not have peritoneal metastasis or positive cytology. Of these patients, 9 patients underwent surgery. R0 resection was achieved in 7 of 9 patients. False-negative results were obtained in two cases because of positive peritoneal cytology.Hospital cooperation may enable us to perform short-term staging laparoscopy. However, false-negative results were obtained in two cases because of positive peritoneal cytology. Further improvement must be made to assure the diagnostic accuracy of this procedure.

It has been reported, as a result of Western blot analyses, that FKBP51 is expressed in various tissues, but that it is not expressed in the pancreas, lung, colon, stomach, or spleen. In this paper, we show, using Western blot analyses, reverse transcriptase polymerase chain reaction, and immunohistochemical analyses of samples from colon cancer patients, that both normal epithelial cells and adenocarcinoma in the human colon express FKBP51, and that there are no significant differences in the expressions of FKBP51 between them. We also show that FKBP51 suppresses the proliferation of colorectal adenocarcinoma, possibly due to the suppression of functions of the glucocorticoid receptors.

Retinal degeneration and dystrophy are the major causes of blindness in the developed world. It has been reported that human cord blood cells (HCBCs) can differentiate into neuron-like cells in vitro. We have recently demonstrated that bone marrow cells (BMCs) of both mice and rats can differentiate into retinal nerve cells (RNCs). In the present study, we show the differentiation capacity of HCBCs into RNCs in vivo. We transplanted lineage-negative HCBCs into the subretinal space of severe combined immunodeficiency (SCID) mice. Two weeks after the transplantation, some of the transplanted cells expressed human nestin, human MAP2, human neuron specific enolase (NSE), beta-III tubulin and also rhodopsin. These results indicate that HCBCs can differentiate into RNCs and suggest that our new strategy could be used for the regeneration of retinal nerve cells in degenerative or dystrophic diseases.

We have previously shown that the combination of allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells is effective in suppressing tumor growth, but that this does not induce graft-versus-host disease (GVHD) in mice. In this report, we show that formalin-fixed tumor cell-pulsed dendritic cells (FFTCP DCs) have an additive effect with IBM-BMT plus DLI on the suppression of tumor growth, but that the DCs do not augment GVHD. BALB/c mice, which had been subcutaneously inoculated with Meth A (BALB/c-derived fibrosarcoma), were irradiated at a low dose (5 Gy) and were transplanted with bone marrow cells (BMCs) from C57BL/6 (B6) mice into the bone marrow cavity (IBM-BMT). Simultaneously, the mice were intravenously injected with spleen cells from B6 mice, and subcutaneously injected with FFTCP DCs derived from the bone marrow (BM) of B6 mice. At the point of the induction of DCs from BMCs, formalin-fixed Meth A cells were added into the culture. The mice treated with the combination of FFTCP DCs, IBM-BMT and DLI using CD4+ cell-depleted spleen cells showed smaller tumor sizes and longer survival than the mice treated with IBM-BMT plus FFTCP DCs or IBM-BMT plus DLI using CD4+ cell-depleted spleen cells. These results suggest that the combination of FFTCP DCs, IBM-BMT plus DLI using CD4+ cell-depleted spleen cells has potent anti-tumor effects without showing GVHD.

We have recently established a novel method for bone marrow transplantation: intra-bone marrow-bone marrow transplantation (IBM-BMT), by which the rapid recovery of donor-derived hematopoiesis can be expected even when reduced radiation doses are used. In this paper, we examine, using mice, whether the combination of pretreatment of recipients with granulocyte-colony-stimulating factor (G-CSF) and IBM-BMT can induce a more rapid recovery of donor-derived hematopoiesis than IBM-BMT alone. We first pretreated recipients with recombinant human (rh) G-CSF (250 microg/kg/day) for 5 consecutive days (days -6 to -2). On day -1, the recipients were irradiated, and IBM-BMT was carried out on day 0. On day 12, we performed colony-forming units of spleen (CFU-S) assays. The combination of G-CSF pretreatment and IBM-BMT augmented the CFU-S counts, the weight of spleens, and the numbers of donor-derived hematopoietic cells. We next analyzed the mechanisms underlying these effects of G-CSF and found that (i) G-CSF induces Th2 polarization, which can prevent graft rejection, and (ii) G-CSF augments natural suppressor activity, which suppresses graft rejection. The combination of G-CSF pretreatment and IBM-BMT can produce the rapid recovery of donor-derived hematopoiesis and suppress graft rejection. This method would lighten the burden on patients in allogeneic BMT.

Low-doses of irradiation have been reported to have beneficial effects, particularly anti-tumor effects. In this paper, we show the effects of the low-dose irradiation on T cell activation induced by dendritic cells (DCs). DCs, which had been pre-irradiated at 0.02-1.0 Gy from a (137)Cs source, were cultured with allogeneic T cells, and the proliferation of T cells was then examined. The 0.05Gy-pre-irradiated DCs showed the highest proliferation capacity of T cells. The 0.05Gy-irradiation does not augment the expression of major histocompatibility complexes (MHCs) or costimulatory molecules on DCs, as with non-irradiated DCs or 1Gy-irradiated DCs, but does augment the production of IL-2, IL-12 and IFN-gamma DCs. These results suggest that the low-dose irradiation augments T cell-activation capacity through cytokine production by DCs, which might shift naive helper T cells to Th1 cells.

G-CSF and M-CSF are used clinically to augment hematopoiesis after bone marrow transplantation (BMT) and chemotherapy. In this paper, we examined the synergistic effect of G-CSF and M-CSF on hematopoietic recovery in allogeneic BMT as a model of human BMT. We performed BMT from eGFP-transgenic mice (C57BL/6 background; H-2 b ) into lethally-irradiated C3H (H-2 k ). From the day after BMT, G-CSF and/or M-CSF were injected for 5 consecutive days. Not only the numbers of day 12 CFU-S and spleen weight, but also white blood cell (WBC) counts in the peripheral blood (PB) and nuclear cells in the bone marrow (BM) increased in the mice treated with G-CSF and/or M-CSF 12 days after BMT. Moreover, the number of donor-type WBCs in the PB and donor-type nuclear cells in the BM also increased in the mice treated with G-CSF and/or M-CSF. The effects were pronounced when G-CSF and M-CSF were used together rather than independently. These results suggest that treatment with the combination of G-CSF and M-CSF has a synergistic effect on hematopoiesis in allogeneic BMT.

It has been reported that granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) can mobilize endothelial progenitor cells (EPCs) in bone marrow cells (BMCs) into peripheral blood (PB) in vivo. Previously, we also reported that macrophage-colony stimulating factor (M-CSF) can mobilize EPCs into PB, which results in the rapid recovery of blood flow in induced-ischemia limbs by augmenting the number of intramuscular capillaries in vivo. In the present study, we demonstrate that M-CSF and/or G-CSF can increase EPCs from lineage (CD3, B220, Gr-1, Mac-1, CD11c, Ter119, NK1.1 or CD31)-negative BMCs in vitro. Lineage-negative BMCs were cultured with or without M-CSF and/or G-CSF. Three days after culture with M-CSF and/or G-CSF, the number of Flk-1+/CD45-, Sca-1+/CD45-, CD31+/CD45- or CD146+/CD45- cells increased in comparison with no cytokines. When the cultured BMCs with or without G-CSF and/or M-CSF were intravenously injected into ischemia-induced hindlimbs of mice, the number of intramuscular capillaries in the ischemia-induced legs increased; BMCs cultured with G-CSF and/or M-CSF were more effective than those of cytokine non-treated BMCs. These results suggest that M-CSF and/or G-CSF can induce the differentiation of BMCs into EPCs, even in vitro.

Recently we reported that macrophage colony-stimulating factor (M-CSF) can mobilize endothelial progenitor cells (EPCs) from the bone marrow into the peripheral blood, resulting in an increase in the number of blood vessels and augmentation of blood flow in the ischemia-induced legs. M-CSF accelerates neovascularization of ischemic lesions resulting from the mobilization of EPCs. In the present paper, we analyze the mechanisms underling the mobilization of EPCs by M-CSF. M-CSF augments the production of vascular endothelial growth factor (VEGF) from the bone marrow cells, especially from myeloid lineage cells. In vivo administration of anti-VEGF antibody abrogates both the acceleration of the recovery of blood flow in the ischemia-induced limbs by M-CSF and the augmentation of the mobilization of EPCs induced by M-CSF. These results suggest that the M-CSF contributes to rapid recovery of blood flow in ischemic lesions by mobilization of EPCs from the bone marrow through augmentation of VEGF production in the bone marrow and that the VEGF is mainly produced by myeloid lineage cells.

At present, there is no curative strategy for advanced cardiomyopathy except for cardiac transplantation, which is not easily performed, mainly due to a shortage of donors. It has been reported that myocardial progenitor cells exist even in the postnatal heart, suggesting that myocardial progenitor cells could proliferate under some situations and might improve cardiac function in cardiomyopathy-induced hearts. In this study, recombinant human hepatocyte growth factor (rhHGF) was delivered using ultrasound-mediated destruction of microbubbles (UMDM) into the cardiomyopathy-induced heart by doxorubicin (20 mg/kg). Intravenous injection of rhHGF (IV-rhHGF) alone or UMDM alone failed to improve the morphology or the function of the cardiomyopathy-induced heart, but (IV-rhHGF + UMDM) treatment significantly improved the heart morphologically and functionally, and repetitive treatments of (IV-rhHGF + UMDM) enhanced the effects. The number of bromodeoxy-uridine-positive cardiomyocytes significantly increased in the (IV-rhHGF + UMDM)–treated hearts compared with the untreated hearts. Moreover, Sca-1+ myocardial progenitor cells express c-Met, a receptor for HGF. These results suggest that (IV-rhHGF + UMDM) treatment could morphologically and functionally improve the heart in the case of doxorubicin-induced cardiomyopathy through the proliferation of the myocardial progenitor cells.

Recently, we have demonstrated that bone marrow stem cells can differentiate into retinal nerve cells. In the present study, we show a new and efficient strategy for transplanting bone marrow stem cells into the retina. When bone marrow stem cells were injected into the vitreous cavity of untreated eyes, only very few cells were found in the retina 2 weeks after injection. In contrast, when laser photocoagulation was performed just before the injection of bone marrow stem cells, a large number of the injected cells survived 2 weeks after injection and the cells expressed neural cell-specific or retinal nerve cell-specific antigens. Moreover, we still detected bone marrow stem cell-derived retinal nerve cells in the retina 1 year after injection in the retina.

We report a patient with diffuse peritoneal metastases of GIST who was administered STI571 (a tyrosine kinase inhibitor). She was a 45-year-old woman who underwent surgery for a mass that was suspected to be an ovarian tumor. The postoperative diagnosis was GIST developing from the small intestine. Two years later, multiple peritoneal metastases were noted and a complete macroscopic resection was done. Six months after the second operation, she needed a third operation and complete macroscopic resection was repeated. Only 4 months after the third operation, she underwent a fourth operation. We resected massive peritoneal metastases, but diffuse metastases remained. Therefore, we started to administer STI571 at 400 mg/day. She has been free from peritoneal masses for 9 months after the fourth operation. We recommend STI571 for uncontrolled diffuse peritoneal metastases of GIST.